The purpose of this Phase II STTR project is to develop a nanoparticle-based drug delivery system for use in the treatment of dry age-related macular degeneration (AMD). AMD is the leading cause of blindness for individuals over fifty-five years of age that live in the industrialized world, affecting approximately 10 million people in the US and as many as 30 million worldwide. There are two forms of the disease, both of which cause a loss of central vision. Approximately fifteen percent have wet, or exudative, AMD, which causes rapid, disabling blindness. The remaining eighty-five percent of patients have dry AMD, a less severe form that produces gradual vision loss. At present, there are no approved pharmacological agents approved for the treatment of dry AMD. This project seeks study to develop a "smart" poly-lactic, glycolic acid (PLGA) nanoparticle drug delivery system that can home to sites of inflammation after intravenous injection. Homing is achieved through a mechanism similar to one used by lymphocytes recognize regions of inflammation. Once there, the particles will release a complement inhibitor over a sustained period time. A growing body of research links excessive complement activation with several diseases of aging, including AMD. The prototype nanoparticle developed in Phase I is able to selectively bind activated endothelial cells in cell culture. In vivo studies further show that the nanoparticles are able to bind inflamed blood vessels in the eye. In vitro studies showed that they are also able to release a complement inhibitor for periods in excess of 60 days. PUBLIC HEALTH RELEVANCE This application is critically concerned with developing a drug product that can be used to treat nonexudative age-related macular degeneration. There are currently no approved treatments for this disorder, making it a major the issue of public health. In the longer term, the goal of this work is to develop drug products that can selectively target and treat sites of disease action, particularly those associated inflammation and degenerative disease. [unreadable] [unreadable] [unreadable]